Association of genetic variation in serum amyloid-A with cardiovascular disease and interactions with IL6, IL1RN, IL1beta and TNF genes in the Cardiovascular Health Study.
Association of genetic variation in serum amyloid-A with cardiovascular disease and interactions with IL6, IL1RN, IL1beta and TNF genes in the Cardiovascular Health Study.
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DOI：
10.5551/jat.no968
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发表时间：
2009-08
影响因子：
4.4
通讯作者：
Reiner AP
中科院分区：
文献类型：
--
作者：
Carty CL;Heagerty P;Heckbert SR;Enquobahrie DA;Jarvik GP;Davis S;Tracy RP;Reiner AP
由于炎症是动脉粥样硬化的重要因素，介导炎症的基因变异引起了人们的兴趣。我们研究了急性期血清淀粉样蛋白A(SAA)的基因变异，以及它们与心血管疾病(CVD)和高密度脂蛋白胆固醇(HDLc)的关系。此外，还探讨了SAA基因与其调节因子IL-1、IL-6和肿瘤坏死因子-α的遗传变异在影响心血管疾病中的相互作用。心血管健康研究的欧洲人(EA)和非裔美国人(AA)参与者(n=3969和n=719)对表征SAA1和SAA2基因常见变异的SNPs进行了基因分型。使用线性和COX比例风险回归，我们评估了SNPs与基线颈动脉内中膜厚度(CIMT)以及发生心肌梗死、缺血性卒中、总心血管事件或14年内死亡率的风险之间的关系。除心血管事件总数外，在EA中未观察到SAA SNPs与预后的关联；在肥胖者中，每个rs4638289微小等位基因与风险增加相关，HR=1.2(95%可信区间：0.98-1.4；p=0.086)，在非肥胖者中，风险降低，HR=0.9(95%CI：0.8-0.99；p=0.026)。在再障患者中，我们观察到SAA SNP和CIMT之间存在适度的关联，这种关联可能会被高密度脂蛋白改变。在EA和AA中，SAA单核苷酸多态也与低密度脂蛋白相关。在随后的模型选择试验中，AA的CIMT和EA的CVD死亡率的基因-基因交互作用结果并不显著。确定了SAA SNPs与CIMT、高密度脂蛋白和总心血管事件的关联，不考虑多次测试。在被其他研究证实之前，这些发现应该被认为是假设产生的。
Since inflammation is an important contributor to atherosclerosis, gene variants mediating inflammation are of interest. We investigated gene variants in acute phase serum amyloid-A (SAA), a sensitive indicator of inflammatory activity, and their associations with cardiovascular disease (CVD) and HDL cholesterol. Interaction of the SAA genes with genetic variants of their regulators, IL-1, IL-6 and TNF-α in influencing CVD was also explored. SNPs characterizing common variation in the SAA1 and SAA2 genes were genotyped in European-(EA) and African-American (AA) participants (n=3969 and n=719) of the Cardiovascular Health Study. Using linear and Cox proportional hazards regression, we assessed associations of SNPs with baseline carotid artery intima-media thickness (cIMT) and risk of incident myocardial infarction, ischemic stroke, total CVD events or mortality during ~14 years of follow-up. No associations between SAA SNPs and outcomes were observed in EA, with the exception of total CVD events; each rs4638289 minor allele was associated with an increased risk in obese individuals, HR=1.2 (95%CI: 0.98-1.4; p=0.086) and decreased risk among non-obese, HR=0.9 (95%CI: 0.8-0.99; p=0.026). In AA, we observed modest associations between SAA SNPs and cIMT, potentially modified by HDL. SAA SNPs were also associated with lower HDL in EA and AA. Suggestive gene-gene interaction findings for cIMT in AA and CVD mortality in EA were not significant in subsequent model selection tests. Associations of SAA SNPs with cIMT, HDL and total CVD events were identified, unadjusted for multiple testing. These findings should be regarded as hypothesis-generating until confirmed by other studies.
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DOI：
10.1161/atvbaha.108.178681
发表时间：
2009-02
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Jahangiri A;de Beer MC;Noffsinger V;Tannock LR;Ramaiah C;Webb NR;van der Westhuyzen DR;de Beer FC
通讯作者：
de Beer FC
影响因子：
8.3
作者：
OLEARY, DH;POLAK, JF;MANOLIO, TA
通讯作者：
MANOLIO, TA
DOI：
10.1161/01.atv.0000248534.30057.b5
发表时间：
2006-12-01
影响因子：
8.7
作者：
Carty, Cara L.;Heagerty, Patrick;Jarvik, Gail P.
通讯作者：
Jarvik, Gail P.
影响因子：
2.1
作者：
Kooperberg, C;Ruczinski, I;Hsu, L
通讯作者：
Hsu, L
影响因子：
6.5
作者：
Abe-Dohmae, Sumiko;Kato, Koichi H.;Yokoyama, Shinji
通讯作者：
Yokoyama, Shinji